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A more recent version of this article appeared on June 27, 2003
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Papers In Press, published online ahead of print April 25, 2003
J. Biol. Chem, 10.1074/jbc.M303424200
Submitted on April 2, 2003
Revised on April 18, 2003
Accepted on April 25, 2003

A novel consensus motif in fibronectin mediates dipeptidyl peptidase IV adhesion and metastasis

Hung-Chi Cheng, Mossaad Abdel-Ghany, and Bendicht U. Pauli

Molecular Medicine, Cancer Biology Laboratories, Cornell University, College of Veterinary Medicine, Ithaca, NY 14853-6401

Corresponding Author: bup1{at}cornell.edu

Lung endothelial dipeptidyl peptidase IV (DPPIV/CD26) is a vascular address for cancer cells decorated with polymeric cell-surface fibronectin (polyFN). Here, we identify the DPPIV-binding sites of FN and examined the effect of binding site-peptides on DPPIV/polyFN adhesion and metastasis. Using proteolytic fragments and maltose-binding protein (MBP)-fusion proteins that together span the full-length of FN, we found DPPIV-binding sites in the 13th, 14th, and 15th type III repeats (FNIII13, FNIII14, FNIII15). DPPIV-binding was mediated by the consensus motif T(I/L)TGLX(P/R)G(T/V)X and was confirmed by swapping this motif in FNIII13, FNIII14, and FNIII15 with the corresponding region in FNIII12, which did not bind DPPIV. DPPIV-binding was lost in swapped FNIII13, FNIII14, and FNIII15 and gained in swapped FNIII12 [FNIII12(14)]. Peptides containing the DPPIV-binding domain of FNIII14 block the DPPIV/polyFN adhesion and impede pulmonary metastasis. This study adds to the classes of cell surface adhesion receptors for FN and will help in a further characterization of the functional implication of the DPPIV/polyFN adhesion in metastasis and, possibly, in cell-mediated immunity involving DPPIV-expressing lymphocytes.


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